Method for monitoring the operational capability of a transport device and liquid transport device

ABSTRACT

In a method for monitoring the operability of a liquid delivery device such as a dispenser ( 10 ), a response signal of a liquid-transformer system consisting of a transformer ( 24 ) and a chamber ( 12 ) containing a liquid is compared with a reference value. Preferably, the reference value is determined when the liquid-transformer system is operative, i.e., non-disturbed. The response signal differs from the reference value if there are air bubbles in the chamber ( 12 ), for example. By comparing the response signal with the reference value, a correction step such as a cleaning cycle can be performed when a limit value is exceeded or fallen short of.

This is a National Phase Application in the United States ofInternational Patent Application No. PCT/EP02/07554 filed Jul. 6, 2002,which claims priority on German Patent Application No. 101 32 530.4,filed Jul. 9, 2001. The entire disclosures of the above patentapplications are hereby incorporated by reference.

The invention relates to a method for monitoring the operability of aliquid delivery device as well as to a liquid delivery device. Liquiddelivery devices, for example, are pipetting or dispensing devices aswell as pumps.

Dispensing and pipetting devices, for example, are used to fill samplecarriers, such as, e.g., titer plates. Such titer plates comprise aplurality of wells, e.g., 1536 or 2080 wells, each well receiving asmall quantity of sample liquid. Thereafter, the samples contained inthe titer plates are analyzed in, e.g., automatic analysis processessuch as the high throughput screening (HTS). A great number of samplesis analyzed in a short time in high throughput screening installationsin particular. Therefore, it is required to automatically fill thesample carriers with sample liquid.

Automatic dispensing or pipetting devices are employed to fill titerplates or other sample carriers. Such liquid delivery devices comprise achamber for receiving liquid. Typically, the pressure in this chamber isincreased to deliver liquid droplets. To this end, for example, apiezoelement is provided which acts upon the liquid provided in thechamber. Thus, liquid is delivered from a dispensing or pipetting tip byapplying a voltage to the piezoelement. Sometimes, the deliveredquantities for filling titer plates comprise only a few nanoliters,particularly less than 50 nl. For filling titer plates with a pluralityof wells, several dispensing or pipetting devices are typically arrangednext to each other and operated in parallel.

The micropumps, i.e., the combination of piezoelements and liquidchamber, are extremely susceptible to failure. Disturbances have aninfluence upon the liquid quantity delivered by the liquid deliverydevice. Particularly upon high throughput screening, even minor changesof the liquid quantity have a considerable influence upon the analysisresults so that the analysis results are considerably falsified and thusbecome useless even with small liquid quantity deviations. Suchdisturbances, e.g., occur because of air bubbles in the chamber orcapillaries connected to the chamber, from which the liquid is deliveredor to which it is supplied. Further, depositions or efflorescences of orfrom the liquid may result in partial or complete cloggings.Disturbances may also be caused by liquid droplets at an outlet openingof the liquid delivery device since the flight direction of the drops ischanged or the drops are not delivered at all. Disturbances may furtheroccur as a result of changing physical properties of the liquid, suchas, e.g., viscosity changes or changes of the composition of the liquid.Furthermore, disturbances may be caused by changing the ambienceconditions, e.g., dipping the pipetting or dispensing tip into liquid.

It is the object of the invention to provide a method for monitoring theoperability of a liquid delivery device by means of which theoperability of the liquid delivery device is improved. Further, it is anobject of the invention to provide a liquid delivery device with animproved operability.

This object is solved, according to the invention, with a methodaccording to claim 1 and a device according to claim 19.

In a liquid delivery device with a liquid receiving portion and atransformer acting upon the liquid in the liquid receiving portion 12,e.g., an electromechanical transformer such as a piezoactuator, aresponse signal produced by a liquid-transformer system in operation isused, according to the invention, to perceive occurring disturbancessuch as air bubbles, cloggings and the like. The response signal may be,e.g., a current, voltage or charge signal. Either a signal directlyemitted by the transformer or a signal obtained by a transform can beused as a response signal. The knowledge forming the basis of theinvention consists in that a liquid-transformer system, i.e., a systemsubstantially consisting of mechanical components of the transformer andof liquid onto which the transformer acts, comprises one or morecharacteristic “fluidic resonances”. This means that at least a part ofthe mass of the liquid covibrates together with the mechanicalcomponents of the transformer and influences the vibrational propertiesin a characteristic manner. The response signal also includes, e.g.,information on faults in fluidic partial systems of theliquid-transformer system. Particularly distinct changes occur at theresonance frequency (frequencies), wherein it is particularly possibleto detect a frequency shift or attenuation. Characteristic changes of aresponse signal, however, can also be detected at other frequencies. Inthis case, e.g., the viscosity and the composition of the liquid ontowhich the transformer acts have to be considered as well.

Due to an inclusion of air, a clogging or changing physical propertiesof the liquid, e.g., the viscosity, the liquid-transformer systemexperiences a change of the vibrating mass. In other words, a responsesignal changes when the liquid-transformer system is excited by anexcitation signal and a disturbance and/or change occurs. The responsesignal also changes when, e.g., the dispensing or pipetting tip, i.e., adelivering tip of the liquid delivery device, is dipped into liquid or adrop clings to the tip. Thereby, a part of the vibrations is transferredto the liquid into which the tip is dipped or the clinging dropincreases the vibrating mass.

According to the method according to the invention, the transformer ofthe liquid-transformer system is excited by an excitation signal. Thisexcitation is effected, for example, at regular time intervals duringoperation. At different times, different excitation signals can be used.Preferably, the excitation signal corresponds to a frequency ofresonance. An excitation signal close to a frequency of resonance isalso preferred. Preferably, the frequency difference between thefrequency of resonance and the excitation signal is twice the half-widthof the resonance at maximum. In the next step, the response signal ofthe liquid-transformer system caused by the excitation signal isacquired. Subsequently, the response signal is compared with a referencevalue. The reference value is, e.g., a preset value or a value stored ina control unit. The comparison between one or more reference values anda response signal can be made directly by means of an appropriateelectronic circuit. It is also possible to compare and evaluate thesignals in digitized form, respectively, with the use of software, ifnecessary. Because of a comparison of the response signal with thereference value, it can be decided whether a malfunction of the liquiddelivery device is given. If this is true, a correction step isperformed.

Preferably, the reference value is a response signal of theliquid-transformer system in which there are no disturbances such ascloggings and the like. This reference value, for example, may be storedin a memory means. Such a reference value is preferably determined bymeasuring the response signal of an operative liquid-transformer systemat a frequency of resonance. This measurement can be performed once andthen, the reference value is stored in the memory means. For checkingpurposes, a corresponding measurement can be repeated at regularintervals. It is also possible to determine a reference value beforeeach measurement. In this embodiment of the method, the correction stepis preferably performed when the response signal exceeds or falls shortof a limit value.

In another preferred embodiment of the method, a response signal of adisturbed liquid-transformer system, i.e., a liquid-transformer systemwith a certain type of clogging, for example, is preset as a referencevalue. This reference value, in turn, may be stored. The reference valuecan be determined, in turn, by measuring a response signal in amalfunctioning liquid-transformer system and storing it in a controlmeans. In this preferred embodiment of the method, the correction stepis preferably performed when the response signal lies within a presetdeviation from the reference value. This means that the response signalsubstantially corresponds to the reference value here so that it cansimultaneously be detected which type of disturbance has occurred, e.g.,whether there is a partial or a complete clogging. Preferably, severalreference values are stored in dependence on occurring disturbancetypes. Different reference values are stored, for example, for acomplete clogging, a partial clogging or a drop clinging to the tip of apipetting or dispensing means. Thus, it is possible to simultaneouslydetect the type of disturbance on the basis of the response signal.

The reference value, which may be the reference value of an operative ora malfunctioning liquid-transformer system of a certain type ofdisturbance, may also be detected by means of substitute models of theliquid-transfer device. It is particularly possible to detect referencevalues by means of computer simulations.

Preferably, a correction step will only be performed when the limitvalue has been exceeded/fallen short of or a response signal within apreset deviation from the reference value has occurred repeatedly, e.g.,within a preset period of time, or in immediate succession. Thus, acorrection step is performed in dependence on statistics.

The liquid delivery pump may also be a pump such as a HPLC pump, forexample. In this case, a response signal can be measured directly at thepump or by a succeeding liquid-transformer system. The reference valueitself may be variable as to time (f(t)), the variation being calculatedor generated as a function of a further measured signal, such as, e.g.,as a function of the relation of acetonitrile/water in case of a HPLCpump. By means of the method according to the invention, it is thuspossible to determine the composition of the HPLC liquids, e.g., inconnection with a preset gradient.

It is also possible, for example, to detect the state of a valve bymeans of the method according to the invention by the use of anadditional liquid-transformer system. As soon as the valve has beenopened, there is liquid in a portion located behind the valve in flowdirection. Thereby, the response signal changes. Thus, the operabilityof a valve can be checked by means of the method according to theinvention. This is particularly advantageous with microsystem chips.

The reference value, e.g., is a value (e.g., input impedance in case ofa frequency), a combination of values (e.g., input impedance in case ofseveral frequencies), a certain limited range of values (partialspectrum (e.g., input impedance between 1000 and 3000 Hz)), an entirespectrum and/or a mathematical function. The reference value can beregarded as a value, i.e., as a single curve, for example, or as atolerance range, i.e., between two curves, for example. Preferably, theresponse signal is determined in a first step at a single frequency fordetermining the error occurred as exactly as possible. This frequency isincluded in the spectrum of the reference value. If the response signalobtained by this frequency does not permit a clear statement as to theerror, the response signal is preferably determined with a combinationof frequencies, ranges of different frequencies (partial spectra) or incorrespondence with the reference value over the entire spectrum.Thereby, it is possible to detect the exact error in question—ifnecessary, in several steps.

The correction step may consist in performing a cleaning step or dabbinga dispensing or pipetting tip. Another example for a correction step isto stop the liquid delivery with or without outputting a correspondingsignal to the user. Then, in dependence on the detected error, forexample, the user may execute a cleaning, a new adjustment or the likeat the liquid delivery device. Further, the detected error value mayalso be stored. Such a storing may be used for statistical evaluationsin order to check whether the detected type of error really correspondsto the actual type of error, etc. It is also possible, for example, toneither change the delivered quantity nor perform a cleaning or the likein a correction step but rather merely store the detected error andcontinue the liquid delivery procedure without any changes. The storingmay be performed, for example, with respect to a particular well sothat, in a future examination of this well, it is known that errors haveoccurred when delivering liquid into this well and thus, the measuredresults might be falsified. Depending on the type of the error occurred,it may be relevant for all the succeeding wells or also for the specificwell only.

The method may be carried out, e.g., at regular intervals during aprocedure of filling titer plates or other sample carriers. It isfurther possible to continuously carry out the method according to theinvention during the entire filling procedure. This is a particularlypreferred embodiment of the method. Preferably, the state of theliquid-transformer system is measured by the signal by which the liquiddelivery device is simultaneously operated. To this end, a signal ischosen which is suitable for exciting the liquid-transformer system andincludes the frequencies at which the response signal is to be measured.In the simplest case, a sinusoidal signal can be used. To guarantee acorresponding actuation of the transformer, the excitation signalcomprises a sufficient amplitude. Thus, it is possible to operate theliquid delivery device as well as to simultaneously carry out a functionmonitoring with one and the same signal.

The method according to the invention has the advantage that noadditional sensor for monitoring the operability of the liquid deliverydevice is required. The monitoring is rather performed directly via apreferably reversible electromechanical transformer such as apiezoactuator of a micropump, which simultaneously operates the liquiddelivery device and performs the operability monitoring as well.Further, a plurality of different errors can be detected by the methodaccording to the invention. Apart from the fact that air or gas bubblescan be detected in the liquid, cloggings, efflorescences and depositionsare detectible as well. As described above, it is also possible todetect a dipping of the liquid delivery tip in a liquid. By means of themethod according to the invention, it is particularly possible to detectphysical changes of the liquid. A change of viscosity caused bytemperature variation, for example, is detected by means of the methodaccording to the invention. By means of the method according to theinvention, it is also possible to detect that a liquid drop clings tothe liquid delivery tip, since the mass of this liquid drop is a part ofthe mass of the liquid-transformer system and thus, a response signal isproduced that differs from the reference value.

The liquid acted upon by the transformer is preferably disposed in achamber, particularly a chamber of a micropump. Typically, the chamberof a micropump comprises an inlet opening of small diameter forsupplying liquid into the chamber. Further, the chamber of a micropumpcomprises an outlet opening that also has a small diameter. Bygenerating pressure in the chamber by means of a piezoactuator, liquidis ejected from the outlet opening. By such pumps, it is possible toeject minimum quantities of liquid in the range of a few nanoliters orless. By micropumps, single drops or a larger quantity of liquid can beejected.

In another preferred embodiment of the invention, the generation of theexcitation signals as well as the reception of the response signal iseffected by means of the transformer. This can be performed by the factthat the transformer generates a pulse as an excitation signal, isswitched to reception mode and is thus able to receive the responsesignal of the system. It is then required, however, that the excitationpulses are very short since the response signal comes very fast becauseof the small size of the system.

In a particularly preferred embodiment, the delivery of the excitationsignal and the reception of the response signal is effectedsimultaneously or may overlap in time at least partially. With anelectric or electromechanical transformer such as a piezoactuator, thismay be effected by applying a voltage to the transformer. Then, theresponse signal of the liquid-transformer system is the current flowingin the transformer, for example. Thus, the response signal is a measurefor the “resistance” the transformer meets upon moving the liquid. Fromthis response signal, i.e., the “transformer resistance”, information ona disturbance such as an air bubble, a clogging of the nozzle or acovibration of a drop hanging in a nozzle etc. can be obtained.Preferably, the response signal is determined by means of the impedance,the capacitance and/or the admittance of the liquid-transformer system.Preferably, the reference value is determined by means of the impedance,the capacitance and/or the admittance of the liquid-transformer systemas well. By means of the electric impedance, e.g., it is easily possibleto detect changes in the phase shift between current and voltage,occurring at malfunctions. The input impedance, the input admittance orthe input capacitance can be used for measuring.

After having detected a malfunction by comparing the reference valuewith the response signal, a cleaning cycle, for example, can be carriedout as a correction step. A cleaning cycle, for example, is thecontinuous delivery of a large liquid quantity. This effects theflushing of air bubbles, depositions and the like from the chamber. If,for example, a change of the viscosity of the liquid is detected by themethod according to the invention, a change of the excitation signal ofthe electromechanical transformer can be effected-as a correction stepas well so that an adaptation of the delivered liquid quantity to thechanged viscosity of the liquid is effected. This results in that aconstant drop volume can also be produced with changing viscosities ofthe liquid. Corresponding excitation signals in dependence on theviscosity are preferably deposited in the memory means.

The different disturbances (air bubbles, depositions, dipping into aliquid) cause a different response signal. Since the response signalscan be differentiated, it is possible to detect the type of error on thebasis of the response signal. It is possible to directly detect the typeof error by a suitable control means in which the different values ofthe response signals with respect to an error type are stored. Thisresults in that by means of the control means, the reactions can bedifferent in dependence on the type of error. If an air bubble wasdetected in the chamber, the chamber could be flushed, for example. If,for example, a drop clinging to the liquid delivery tip was detected, itwould be possible to simply and effectively rectify the error by dabbingthe liquid delivery device on an absorbent cloth or the like.

Further, the method according to the invention is also suitable, e.g.,for the monitoring of pumps, particularly HPLC pumps. Here, it ispossible not only to monitor the operability of the pump but also tocontrol the pump itself by means of the method according to theinvention. When the method according to the invention is employed inconnection with pumps, particularly HPLC pumps, a monitoring of thegradient in the HPLC pump is possible. Here, a change of the compositionof the liquid because of contamination or the like is detected as amalfunction. As a correction step, the respective pumps of the liquidscan here be controlled differently to readjust the gradient.

In a preferred embodiment of the method according to the invention, itis possible to not only provide the excitation signal as a singleexcitation frequency but as a signal comprising several excitationfrequencies, e.g., as a square wave signal. Thereby, it is possible toaccommodate several points, partial spectra or an entire spectrum of theresponse signal. Then, for example, different combinations offrequencies or signals can also be significant for different types oferrors.

For exciting the liquid-transformer system for receiving the responsesignal, it is further possible not to use the same means as thatproducing the signal acting upon the transformer but to providedifferent means. The excitation of the liquid-transformer signal, forexample, may be effected electrically or magnetically via a transformerand the acquisition of the response signal can be effected mechanicallyor optically. Furthermore, it is possible that the transformer for theliquid delivery and the function monitoring is not identical.

Further, the invention relates to a liquid delivery device beingparticularly suitable for delivering minimum quantities. The liquiddelivery device comprises a liquid receiving portion, such as, forexample, the chamber of a micropump. Further, the liquid delivery devicecomprises a transformer acting upon the liquid provided in the liquidreceiving portion. The transformer is, for example, a reversibletransformer, preferably an electromechanical transformer, such as apiezoactuator. In further preferred embodiments, it is, for example, amagnetorestrictive transformer. Further, the liquid delivery devicecomprises a control means connected with the transformer. The controlmeans serves to excite the transformer with an excitation signal.Further, the control means preferably also serves to acquire a responsesignal of the liquid-transformer system. It is a response signal to theexcitation signal. Further, the control means serves to compare areference value with the response signal. As described above, thereference value may be, for example, a value or a combination of valuesetc. of an operative or a malfunctioning system. Preferably, it isstored in the control means.

The liquid-transformer system comprises the transformer and the liquidreceiving portion. Substantial for the invention is that the liquidreceiving portion is also considered to be a portion having influenceupon the response signal. Further, all the other covibrating portions ofthe liquid-transformer system have influence upon the response signal.

In a particularly preferred embodiment, the transformer simultaneouslyacts as an actuator and as a sensor. As described above with respect tothe method according to the invention, the generation of the excitationsignal as well as the reception of the response signal may be effectedwith a time offset or preferably simultaneously or in an overlappingmanner. Here, it is particularly preferred to determine the inputimpedance, the input capacitance and/or the input admittance of thetransformer. If necessary, the response signal is carried out by meansof a software or the comparison between the response signal and thereference signal is made by means of a software to be able to detecteven extremely minor changes. With droplets clinging to the nozzle orwith partial cloggings, for example, the input impedance changes areonly extremely small. In this case, it is advantageous to favorablyselect the frequency at which the comparison of the response signal withthe reference value is made in dependence on the liquid-transformersystem. Particularly the measuring parameter has to be chosenadvantageously. The phase values have proven to be advantageousmeasuring parameters.

The liquid delivery device according to the invention is particularlysuitable for carrying out the above method. The respective components ofthe liquid delivery device according to the invention and particularlythe control means are configured such that they are suitable forcarrying out the above method and particularly the preferredembodiments.

Hereinafter, the invention is described in detail with respect topreferred embodiments with reference to the accompanying drawings.

In the Figures:

FIG. 1 shows a schematic front view of a liquid delivery device,

FIG. 2 shows a schematic lateral view of the liquid delivery deviceillustrated in FIG. 1,

FIG. 3 shows a schematic circuit diagram for carrying out the methodaccording to the invention,

FIG. 4 shows signal courses of the reference value and the responsesignal upon occurrence of an air bubble, and

FIG. 5 shows signal courses of the reference value and of responsesignals upon occurrence of a clogging.

In the illustrated embodiment, a dispensing device 10 is illustrated asa liquid delivery device. It comprises a chamber 12 filled with sampleliquid. Via a channel 14, the chamber is connected with a reservoir. Ata dispensing tip 16, an outlet opening 18 is connected with the chamber12 via a capillary 20.

A rear wall 22 of the chamber 12 has a flexible configuration. Apiezoactuator 24 is provided adjacent to the rear wall 22. Via a line26, the piezoactuator is connected with a control means 28. Thepiezoactuator 24 can be activated by the control means 28. By activatingthe piezoactuator, pressure is exerted on the flexible rear wall 22 ofthe chamber 12. Because of the pressure increase in the chamber 12,droplets 30 are ejected from the outlet opening.

The control means 28 preferably is a computer (FIG. 3). The function ofthe control means 28 may as well be taken over by a computer carryingout other objects as well. To this end, the computer 28 comprises atransformer, e.g., a transformer card, consisting of a D-A converter 32and an A-D converter 34. Thus, the D-A converter 32 converts a signal 36produced by the computer 28 into an analogous signal 38 amplified by anamplifier 40 and subsequently supplied to the piezoactuator 24. Thesignal 38 is a signal including the excitation signal. The voltage ofthe signal 38 is either selected such that only the operatibilitymonitoring is performed or a droplet delivery through the outlet opening18 of the pipetting tip 16 (FIG. 1) is simultaneously performed as well.

By means of a measuring resistor 42, a response signal 44 is supplied tothe control means 28 via the A-D converter 34. The response signal isthe response signal of the liquid-transformer system, i.e., the responsesignal particularly caused by the transformer 24 as well as by theliquid in the chamber 12 and all the liquid communicating therewith(e.g., capillaries 20, drops at the nozzle etc.) The other mechanicalparts of the liquid-transformer system, such as, for example, thediaphragm and the capillary 20, have an influence on the responsesignal. In the operational state, i.e., during the monitoring of theoperability, the response signal 44 is the response signal. Before, thereference value is produced with the same circuit illustrated in FIG. 3and stored in the control means 28. Upon producing the reference value,it must be paid attention to that there are no contaminations, airbubbles and the like in the chamber 12 or capillaries 20.

The diagram illustrated in FIG. 4 shows the complex input capacitance ofa dispenser as a function of the frequency. Here, the upper diagramshows the amount of the capacitance as a function of the frequency andthe lower diagram shows the phase of the capacitance as a function ofthe frequency. Both diagrams are obtained from the signals by Fouriertransform. Of course, further mathematical moment analyses andtransforms such as, for example, Laplace analyses, moment analyses,correlation analyses, wavelet analyses etc. are possible as well. In theexperiment illustrated herein, water was used as liquid. The excitationvoltage supplied to the transformer 24 was 10 Volt. Thus, no liquid wasdelivered because liquid is only delivered as of a voltage of about 25V. In an operative liquid-transformer system, i.e., withoutdisturbances, such as air bubbles in the chamber 12, the curve 46 isproduced. Thus, this curve can be regarded as reference value. Whenthere is an air bubble in the region of the capillary 20 connecting theoutlet opening 18 with the chamber 12, the curve 46 is produced. Thus,this curve can be regarded as a reference value. In case of a small airbubble in the chamber 12, the curve 50 is produced. The resonancefrequency illustrated by a line 52 amounts to about 3000 Hz in theillustrated example.

In order to detect a disturbance—an air bubble in the present example—aliquid-transformer system is excited by a signal including the frequencyto be analyzed. In the present example, the signal may include afrequency of about 3000 Hz corresponding to the line 52. Subsequently,the complex capacitance from the time signal is analyzed by Fouriertransform. At least, this analysis must be effected at the frequency ofinterest 52. At the resonance frequency (line 52), the curve 46, i.e.,the curve of an operative non-disturbed liquid-transformer system isbelow a limit value φ_(s) illustrated by the line 54. The phase anglesof the two curves 48,50 representing the response signals in case ofdisturbing air bubbles lie above the limit value φ_(s). As is clearlyapparent from the lower diagram of FIG. 4, the phase shifts of the twocurves 48,50 also differ strongly from each other. Thus, it is possibleto detect the type of the disturbance on the basis of the amount of thephase shift. Then, the control means 28 may perform a cleaning cycle, adabbing of the dispenser tip 16 or the like in dependence on the type ofdisturbance.

Two diagrams corresponding to those of FIG. 4 are represented in FIG. 5.The experiment evaluated by means of the diagrams in FIG. 5 is anintentionally caused clogging of the capillary 20 (FIG. 1). The curve 46corresponds to the curve 46 in FIG. 4 and thus represents the responsesignal of an operative liquid-transformer system without clogging orother disturbance and thus, it can be regarded as a reference value. Thecurve 56 represents a locking of the capillary by 2.6% of thecross-sectional area. The curve 58 represents a locking of the capillary20 by 16% of the cross-sectional area. At the same limit value φ_(s) andthe same resonance frequency, which are illustrated by the lines 52 and54, respectively, the reference value (curve 46) is compared with theresponse signal (curve 56 or 58) again. Therefrom, it is clearlyapparent that the clogging can be definitely detected. On the basis ofthe amount of the phase shift, even the size of the clogging can bedetected. Thus, e.g., a value can be stored where the dispensing must beinterrupted since the clogging is to large to be remedied by a flushingprocedure.

As can be seen from the diagrams in FIGS. 4 and 5, the signals ofmalfunctioning and operative liquid-transformer systems not only differin the resonance frequency but also in other frequencies. Therefore, itis also possible to read out other frequencies and draw conclusionstherefrom as to the type of disturbance. Further, response signals ofseveral frequencies can be monitored simultaneously and from acombination of several frequencies, with respect to a limit value orother reference values, conclusions as to the type of error can bedrawn. Thereby, for example, a detailed determination of the type oferror as well as an increase in the security that the right error hasbeen determined is possible. In FIG. 4, for example, considerabledeviations of the capacitance and the phase, respectively, can also bedetected at a frequency of about 9000 Hz.

1. Method for monitoring the operability of a liquid delivery deviceadapted to be employed for delivering chemical and/or biologicalliquids, comprising the step of: supplying a liquid receiving portionand a transformer acting on the liquid in the liquid receiving portion,exciting the transformer with an excitation signal, acquiring a responsesignal caused by the excilation signal of the liquid-transformer system,comparing the response signal with a reference value, and performing acorrection step depending on the result of the comparison, wherein heexcitation signal also serves as a signal by which the liquid deliverydevice is simultaneously operated to deliver liquid.
 2. The method ofclaim 1, wherein the reference value is the response signal of theoperative liquid-transformer system.
 3. The method of claim 2, whereinthe reference value is determined by measuring the response signal of anoperative liquid-transformer system at or near a resonance frequency. 4.The method of claim 1, wherein the correction step is performed when alimit value (φ_(s)) is exceeded or fallen short of.
 5. The method ofclaim 1, wherein the reference value is the response signal of amalfunctioning liquid-transformer system.
 6. The method of claim 5,wherein the reference value is determined by measuring the responsesignal of a malfunctioning liquid-transformer system at or near aresonance frequency.
 7. The method of claim 1, wherein the correctionstep is performed when the response signal lies within a presetdeviation of the reference value.
 8. The method of claim 1, whereindifferent reference values are stored in the control means in dependenceon the type of disturbance occurring.
 9. The method of claim 1, whereinthe reference values are determined by means of a mathematicalsubstitute model of the liquid delivery device or by means of computersimulation.
 10. The method of claim 1, wherein the correction step isperformed after the limit value (φ_(s)) has been exceeded/fallen shortof repeatedly or a response signal within the preset deviation from thereference value has occurred repeatedly.
 11. The method of claim 1,wherein the reference value is a function in dependence on time.
 12. Themethod of claim 1, wherein the liquid onto which the transformer acts isdisposed in a chamber and/or capillary.
 13. The method of claim 1,wherein the response signal and/or the reference value are determined bymeans of the impedance of the liquid-transformer system.
 14. The methodof claim 1, wherein the response signals are determined by means of amathematical transform.
 15. The method of claim 14, wherein theamplitudes and/or phase shifts of the response signals are compared. 16.The method of claim 1, wherein the type of error is determined on thebasis of the response signal.
 17. The method of claim 1, wherein theexcitation signal and the response signal are overlaid on each other intime at least partially.
 18. A liquid delivery device, particularly forthe delivery of minimum quantities of chemical and/or biologicalliquids, comprising a liquid receiving portion, a transformer acting onthe liquid, and a control means connected with the transformer, forexciting the transformer with an excitation signal, for acquiring aresponse signal of the liquid-transformer system and for comparing areference value with the response signal, wherein the response signalsent by the liquid-transformer system is caused by the excitationsignal, and wherein the excitation signal also serves as a signal bywhich the liquid delivery device is simultaneously operated to deliverliquid.
 19. The liquid delivery device of claim 18, characterized inthat the liquid transformer system producing the response signalcomprises the transformer as well as the liquid in the liquid receivingportion.
 20. The liquid delivery device of claim 18, characterized inthat a reference value is stored in the control means.
 21. The liquiddelivery device of claim 20, characterized in that the reference valueis stored in dependence on the liquid properties and/or liquid quantityon which the transformer acts.
 22. The liquid delivery device of claim18, characterized in that in the control means, response signals arestored each of which has a type of error allocation thereto.
 23. Theliquid delivery device of claim 18, characterized in that thetransformer acts as an actuator and as a sensor at the same time.